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Applied Microbiology and Biotechnology Oct 2023Carboxylic acids containing acidic groups with additional keto/hydroxyl-groups or unsaturated bond have displayed great applicability in the food, agricultural,... (Review)
Review
Carboxylic acids containing acidic groups with additional keto/hydroxyl-groups or unsaturated bond have displayed great applicability in the food, agricultural, cosmetic, textile, and pharmaceutical industries. The traditional approach for carboxylate production through chemical synthesis is based on petroleum derivatives, resulting in concerns for the environmental complication and energy crisis, and increasing attention has been attracted to the eco-friendly and renewable bio-based synthesis for carboxylate production. The efficient and specific export of target carboxylic acids through the microbial membrane is essential for high productivity, yield, and titer of bio-based carboxylates. Therefore, understanding the characteristics, regulations, and efflux mechanisms of carboxylate transporters will efficiently increase industrial biotechnological production of carboxylic acids. Several transporters from fungi have been reported and used for improved synthesis of target products. The transport activity and substrate specificity are two key issues that need further improvement in the application of carboxylate transporters. This review presents developments in the structural and functional diversity of carboxylate transporters, focusing on the modification and regulation of carboxylate transporters to alter the transport activity and substrate specificity, providing new strategy for transporter engineering in constructing microbial cell factory for carboxylate production. KEY POINTS: • Structures of multiple carboxylate transporters have been predicted. • Carboxylate transporters can efficiently improve production. • Modification engineering of carboxylate transporters will be more popular in the future.
Topics: Carboxylic Acids; Membrane Transport Proteins; Biological Transport; Biotechnology; Metabolic Engineering
PubMed: 37561180
DOI: 10.1007/s00253-023-12720-z -
Advances in Experimental Medicine and... 2019Blood-retinal barrier (BRB) includes inner BRB (iBRB) and outer BRB (oBRB), which are formed by retinal capillary endothelial (RCEC) cells and by retinal pigment... (Review)
Review
Blood-retinal barrier (BRB) includes inner BRB (iBRB) and outer BRB (oBRB), which are formed by retinal capillary endothelial (RCEC) cells and by retinal pigment epithelial (RPE) cells in collaboration with Bruch's membrane and the choriocapillaris, respectively. Functions of the BRB are to regulate fluids and molecular movement between the ocular vascular beds and retinal tissues and to prevent leakage of macromolecules and other potentially harmful agents into the retina, keeping the microenvironment of the retina and retinal neurons. These functions are mainly attributed to absent fenestrations of RCECs, tight junctions, expression of a great diversity of transporters, and coverage of pericytes and glial cells. BRB existence also becomes a reason that systemic administration for some drugs is not suitable for the treatment of retinal diseases. Some diseases (such as diabetes and ischemia-reperfusion) impair BRB function via altering tight junctions, RCEC death, and transporter expression. This chapter will illustrate function of BRB, expressions and functions of these transporters, and their clinical significances.
Topics: Blood-Retinal Barrier; Gene Expression; Humans; Membrane Transport Proteins; Retina; Retinal Diseases; Tight Junctions
PubMed: 31571172
DOI: 10.1007/978-981-13-7647-4_10 -
Nature Structural & Molecular Biology Jul 2019Monoamine transporters (MATs) regulate neurotransmission via the reuptake of dopamine, serotonin and norepinephrine from extra-neuronal regions and thus maintain... (Review)
Review
Monoamine transporters (MATs) regulate neurotransmission via the reuptake of dopamine, serotonin and norepinephrine from extra-neuronal regions and thus maintain neurotransmitter homeostasis. As targets of a wide range of compounds, including antidepressants, substances of abuse and drugs for neuropsychiatric and neurodegenerative disorders, their mechanism of action and their modulation by small molecules have long been of broad interest. Recent advances in the structural characterization of dopamine and serotonin transporters have opened the way for structure-based modeling and simulations, which, together with experimental data, now provide mechanistic understanding of their transport function and interactions. Here we review recent progress in the elucidation of the structural dynamics of MATs and their conformational landscape and transitions, as well as allosteric regulation mechanisms.
Topics: Allosteric Regulation; Animals; Binding Sites; Dopamine Plasma Membrane Transport Proteins; Drug Discovery; Humans; Models, Molecular; Norepinephrine Plasma Membrane Transport Proteins; Protein Conformation; Serotonin Plasma Membrane Transport Proteins
PubMed: 31270469
DOI: 10.1038/s41594-019-0253-7 -
Trends in Plant Science Mar 2022Auxin is a key regulator of many developmental processes in land plants and plays a strikingly similar role in the phylogenetically distant brown seaweeds. Emerging... (Review)
Review
Auxin is a key regulator of many developmental processes in land plants and plays a strikingly similar role in the phylogenetically distant brown seaweeds. Emerging evidence shows that the PIN and PIN-like (PILS) auxin transporter families have preceded the evolution of the canonical auxin response pathway. A wide conservation of PILS-mediated auxin transport, together with reports of auxin function in unicellular algae, would suggest that auxin function preceded the advent of multicellularity. We find that PIN and PILS transporters form two eukaryotic subfamilies within a larger bacterial family. We argue that future functional characterisation of algal PIN and PILS transporters can shed light on a common origin of an auxin function followed by independent co-option in a multicellular context.
Topics: Biological Transport; Indoleacetic Acids; Membrane Transport Proteins; Plants
PubMed: 34716098
DOI: 10.1016/j.tplants.2021.09.008 -
Journal of Molecular Biology Aug 2021The synthesis, folding, and function of membrane transport proteins are critical factors for defining cellular physiology. Since the stability of these proteins evolved... (Review)
Review
The synthesis, folding, and function of membrane transport proteins are critical factors for defining cellular physiology. Since the stability of these proteins evolved amidst the lipid bilayer, it is no surprise that we are finding that many of these membrane proteins demonstrate coupling of their structure or activity in some way to the membrane. More and more transporter structures are being determined with some information about the surrounding membrane, and computational modeling is providing further molecular details about these solvation structures. Thus, the field is moving towards identifying which molecular mechanisms - lipid interactions, membrane perturbations, differential solvation, and bulk membrane effects - are involved in linking membrane energetics to transporter stability and function. In this review, we present an overview of these mechanisms and the growing evidence that the lipid bilayer is a major determinant of the fold, form, and function of membrane transport proteins in membranes.
Topics: Cell Membrane; Lipid Bilayers; Membrane Transport Proteins; Models, Molecular; Protein Folding; Structure-Activity Relationship
PubMed: 34139219
DOI: 10.1016/j.jmb.2021.167103 -
Molecular Microbiology Apr 2021Both isomeric forms of alanine play a crucial role in bacterial growth and viability; the L-isomer of this amino acid is one of the building blocks for protein...
Both isomeric forms of alanine play a crucial role in bacterial growth and viability; the L-isomer of this amino acid is one of the building blocks for protein synthesis, and the D-isomer is incorporated into the bacterial cell wall. Despite a long history of genetic manipulation of Bacillus subtilis using auxotrophic markers, the genes involved in alanine metabolism have not been characterized fully. In this work, we genetically characterized the major enzymes involved in B. subtilis alanine biosynthesis and identified an alanine permease, AlaP (YtnA), which we show has a major role in the assimilation of D-alanine from the environment. Our results provide explanations for the puzzling fact that growth of B. subtilis does not result in the significant accumulation of extracellular D-alanine. Interestingly, we find that in B. subtilis, unlike E. coli where multiple enzymes have a biochemical activity that can generate alanine, the primary synthetic enzyme for alanine is encoded by alaT, although a second gene, dat, can support slow growth of an L-alanine auxotroph. However, our results also show that Dat mediates the synthesis of D-alanine and its activity is influenced by the abundance of L-alanine. This work provides valuable insights into alanine metabolism that suggests that the relative abundance of D- and L-alanine might be linked with cytosolic pool of D and L-glutamate, thereby coupling protein and cell envelope synthesis with the metabolic status of the cell. The results also suggest that, although some of the purified enzymes involved in alanine biosynthesis have been shown to catalyze reversible reactions in vitro, most of them function unidirectionally in vivo.
Topics: Alanine; Amino Acid Transport Systems; Bacillus subtilis; Bacterial Proteins; Biosynthetic Pathways; Membrane Transport Proteins; Transaminases
PubMed: 33155333
DOI: 10.1111/mmi.14640 -
Biochemical Society Transactions Dec 2016Transporters are integral membrane proteins with central roles in the efficient movement of molecules across biological membranes. Many transporters exist as oligomers... (Review)
Review
Transporters are integral membrane proteins with central roles in the efficient movement of molecules across biological membranes. Many transporters exist as oligomers in the membrane. Depending on the individual transport protein, oligomerization can have roles in membrane trafficking, function, regulation and turnover. For example, our recent studies on UapA, a nucleobase ascorbate transporter, from Aspergillus nidulans, have revealed both that dimerization of this protein is essential for correct trafficking to the membrane and the structural basis of how one UapA protomer can affect the function of the closely associated adjacent protomer. Here, we review the roles of oligomerization in many particularly well-studied transporters and transporter families.
Topics: Biological Transport; Cell Membrane; Fungal Proteins; Kinetics; Membrane Transport Proteins; Models, Molecular; Mutation; Protein Conformation; Protein Multimerization
PubMed: 27913684
DOI: 10.1042/BST20160217 -
World Journal of Microbiology &... Jul 2020The phosphoenolpyruvate-dependent glucose phosphotransferase system (PTS) is the major uptake system responsible for transporting glucose, and is involved in glucose... (Review)
Review
The phosphoenolpyruvate-dependent glucose phosphotransferase system (PTS) is the major uptake system responsible for transporting glucose, and is involved in glucose translocation and phosphorylation in Corynebacterium glutamicum. For the longest time, the PTS was considered as the only uptake system for glucose. However, some PTS-independent glucose uptake systems (non-PTS) were discovered in recent years, such as the coupling system of inositol permeases and glucokinases (IPGS) and the coupling system of β-glucoside-PTS permease and glucokinases (GPGS). The products (e.g. lysine, phenylalanine and leucine) will be increased because of the increasing intracellular level of phosphoenolpyruvate (PEP), while some by-products (e.g. lactic acid, alanine and acetic acid) will be reduced when this system become the main uptake pathway for glucose. In this review, we survey the uptake systems for glucose in C. glutamicum and their composition. Furthermore, we summarize the latest research of the regulatory mechanisms among these glucose uptake systems. Detailed strategies to manipulate glucose uptake system are addressed based on this knowledge.
Topics: Bacterial Proteins; Biological Transport; Carbohydrate Metabolism; Corynebacterium glutamicum; Glucose; Glucosides; Membrane Proteins; Membrane Transport Proteins; Mutagenesis, Site-Directed; Phosphoenolpyruvate Sugar Phosphotransferase System; Protein Kinases
PubMed: 32712859
DOI: 10.1007/s11274-020-02898-z -
Sub-cellular Biochemistry 2022ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins in prokaryotic organisms. Much is now understood about the structure of...
ATP-binding cassette (ABC) transporters are one of the largest families of membrane proteins in prokaryotic organisms. Much is now understood about the structure of these transporters and many reviews have been written on that subject. In contrast, less has been written on the assembly of ABC transporter complexes and this will be a major focus of this book chapter. The complexes are formed from two cytoplasmic subunits that are highly conserved (in terms of their primary and three-dimensional structures) across the whole family. These ATP-binding subunits give rise to the name of the family. They must assemble with two transmembrane subunits that will typically form the permease component of the transporter. The transmembrane subunits have been found to be surprisingly diverse in structure when the whole family is examined, with seven distinct folds identified so far. Hence nucleotide-binding subunits appear to have been bolted on to a variety of transmembrane platforms during evolution, leading to a greater variety in function. Furthermore, many importers within the family utilise a further external substrate-binding component to trap scarce substrates and deliver them to the correct permease components. In this chapter, we will discuss whether assembly of the various ABC transporter subunits occurs with high fidelity within the crowded cellular environment and whether promiscuity in assembly of transmembrane and cytoplasmic components can occur. We also discuss the new AlphaFold protein structure prediction tool which predicts a new type of transmembrane domain fold within the ABC transporters that is associated with cation exporters of bacteria and plants.
Topics: ATP-Binding Cassette Transporters; Adenosine Triphosphate; Membrane Transport Proteins; Nucleotides; Prokaryotic Cells
PubMed: 36151373
DOI: 10.1007/978-3-031-00793-4_2 -
Research in Microbiology 2018
Topics: Bacteria; Bacterial Proteins; Membrane Transport Proteins
PubMed: 30223033
DOI: 10.1016/j.resmic.2018.09.001